Importance of fiberoptic bronchoscopy in identifying asthma phenotypes to direct personalized therapy.

Divisions of Pulmonary and Critical Care Medicine, Department of Medicine, National Jewish Health, University of Colorado Denver, Denver, Colorado, USA.
Current opinion in pulmonary medicine (Impact Factor: 2.96). 01/2013; 19(1):42-8. DOI: 10.1097/MCP.0b013e32835a5bdc
Source: PubMed

ABSTRACT This review summarizes the phenotyping of refractory asthma with an emphasis on how direct bronchoscopic observation and analysis of bronchoalveolar lavage (BAL), biopsy, and brushings of the airways helps direct specific personalized therapy. Additional testing used in phenotyping asthmatic patients is reviewed.
Several studies and publications over the past decade have emphasized the importance of phenotyping refractory asthmatic patients to offer a better understanding of the pathobiology of disease. Bronchoscopy is a useful tool in phenotyping asthma with objective data obtained from BAL, endobronchial biopsy, and brushings. Phenotyping asthma with bronchoscopy affords personalized and successful therapy.
By using fiberoptic bronchoscopy, specific asthma phenotypes can be identified: laryngopharyngeal reflux with silent aspiration; subacute bacterial infection; tissue eosinophilia; a combination of two or three of these; and nonspecific. Identifying these phenotypes and personalizing therapy with bronchoscopy leads to improved outcomes.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Asthma is characterized by recurrent and reversible airflow obstruction, which is routinely monitored by history and physical examination, spirometry and home peak flow diaries. As airway inflammation is central to asthma pathogenesis, its monitoring should be part of patient management plans. Fractional exhaled nitric oxide level (FeNO) is the most extensively studied biomarker of airway inflammation, and FeNO references were higher in Chinese (Asians) than Whites. Published evidence was inconclusive as to whether FeNO is a useful management strategy for asthma. Other biomarkers include direct (histamine, methacholine) and indirect (adenosine, hypertonic saline) challenges of bronchial hyperresponsiveness (BHR), induced sputum and exhaled breath condensate (EBC). A management strategy that normalized sputum eosinophils among adult patients resulted in reductions of BHR and asthma exacerbations. However, subsequent adult and pediatric studies failed to replicate these benefits. Asthma phenotypes as defined by inflammatory cell populations in sputum were also not stable over a 12-month period. A recent meta-analysis concluded that induced sputum is not accurate enough to be applied in routine monitoring of childhood asthma. There is poor correlation between biomarkers that reflect different asthma dimensions: spirometry (airway caliber), BHR (airway reactivity) and FeNO or induced sputum (airway inflammation). Lastly, EBC is easily obtained noninvasively by cooling expired air. Many biomarkers ranging from acidity (pH), leukotrienes, aldehydes, cytokines to growth factors have been described. However, significant overlap between groups and technical difficulty in measuring low levels of inflammatory molecules are the major obstacles for EBC research. Metabolomics is an emerging analytical method for EBC biomarkers. In conclusion, both FeNO and induced sputum are useful asthma biomarkers. However, they will only form part of the clinical picture. Longitudinal studies with focused hypotheses and well-designed protocols are needed to establish the roles of these biomarkers in asthma management. The measurement of biomarkers in EBC remains a research tool.
    Therapeutic Advances in Respiratory Disease 08/2013; 7(5). DOI:10.1177/1753465813496863
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective Bronchial thermoplasty (BT) reduces airway smooth muscle in patients with severe asthma. We developed a novel standardized histologic grading system assessing inflammation and structural remodeling on endobronchial biopsy (EBBx) in severe persistent asthma and evaluated airway structure before and after BT. In addition, we correlated invasive and non-invasive inflammatory markers in severe persistent asthma. Methods Thirty-three patients with severe persistent asthma underwent bronchoscopy, including bronchoalveolar lavage and diagnostic EBBx. The control group (N=41) underwent EBBx for other clinical indications. Biopsies were graded for airway inflammation and epithelial and submucosal structural features. We also evaluated airway histology in three patients before and after BT. Results Compared to the control group, patients with severe persistent asthma more often had intraepithelial eosinophils and lymphocytes (67% vs. 17% and 61% vs. 27%; p<0.001 and p=0.005, respectively) and prominent smooth muscle and goblet cell hyperplasia (88% vs. 29% and 47% vs. 22%, p<0.001 and p=0.004, respectively). Other features including epithelial denudation and basement membrane thickening were not significantly different. Following BT, airway smooth muscle was no longer prominent due to partial replacement by fibrosis. Increased submucosal eosinophilic inflammation and bronchoalveolar lavage eosinophilia correlated with exhaled nitric oxide (eNO, p=0.05 for both). Conclusions We developed a clinically applicable standardized histologic grading system which identified structural but not inflammatory changes before and after bronchial thermoplasty in severe persistent asthmatics. Additionally, we demonstrate that eNO is representative of submucosal eosinophilia in this population. This semi-quantitative assessment will be useful for practicing pathologists assessing EBBx from severe persistent asthma patients for diagnostic and clinical research purposes.
    Journal of Asthma 04/2013; DOI:10.3109/02770903.2013.794239 · 1.83 Impact Factor